Polycystic kidney disease 2

Summary

Polycystic kidney disease 2 (MONDO:0013131) is a disease caused by PKD2 (GenCC Strong), with 6 cohort genes.

At a glance

• Causal gene: PKD2 (GenCC Strong)
• Cohort genes: 6
• ClinVar variants: 716

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polycystic kidney disease 2
Mondo ID	MONDO:0013131
OMIM	613095
DOID	DOID:0110859
NCIT	C123166
SNOMED CT	253879006
UMLS	C2751306
MedGen	442699
GARD	0018599
Is cancer (heuristic)	no

Also known as: APKD2 · autosomal dominant polycystic kidney disease caused by mutation in PKD2 · Autosomal dominant polycystic kidney disease type 2 · PKD2 · PKD2 autosomal dominant polycystic kidney disease · polycystic kidney disease 2 · polycystic kidney disease type 2

Data availability: 716 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant polycystic kidney disease › polycystic kidney disease 2

Related subtypes (6): polycystic kidney disease 1, polycystic kidney disease 3 with or without polycystic liver disease, polycystic kidney disease 7, polycystic kidney disease 6 with or without polycystic liver disease, ALG9-associated autosomal dominant polycystic kidney disease, polycystic kidney disease 8

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

231 uncertain significance, 201 pathogenic, 53 likely pathogenic, 45 conflicting classifications of pathogenicity, 27 pathogenic/likely pathogenic, 19 likely benign, 17 benign/likely benign, 6 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1699915	NC_000004.12:g.(?88928831)(88996847_?)del	FAM13A	Pathogenic	criteria provided, single submitter
1179063	NM_000297.4(PKD2):c.110del (p.Gly37fs)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
1256457	NM_000297.4(PKD2):c.469C>T (p.Arg157Ter)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
2683951	NM_000297.4(PKD2):c.316del (p.Glu106fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3061900	NM_000297.4(PKD2):c.339_358dup (p.Pro120delinsArgTrpThrTer)	LOC129992813	Pathogenic	criteria provided, single submitter
3235148	NM_000297.4(PKD2):c.325G>T (p.Gly109Ter)	LOC129992813	Pathogenic	criteria provided, single submitter
3235194	NM_000297.4(PKD2):c.423_430dup (p.Tyr144fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3235228	NM_000297.4(PKD2):c.548del (p.Gln183fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3235981	NM_000297.4(PKD2):c.354del (p.Trp118fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3248537	NM_000297.4(PKD2):c.210_211del (p.Ala71fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3255007	NM_000297.4(PKD2):c.566G>A (p.Trp189Ter)	LOC129992813	Pathogenic	criteria provided, single submitter
3338385	NM_000297.4(PKD2):c.592C>T (p.Arg198Ter)	LOC129992813	Pathogenic	criteria provided, single submitter
3374736	NM_000297.4(PKD2):c.478C>T (p.Gln160Ter)	LOC129992813	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376972	NM_000297.4(PKD2):c.354G>A (p.Trp118Ter)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
3377082	NM_000297.4(PKD2):c.298G>T (p.Glu100Ter)	LOC129992813	Pathogenic	criteria provided, single submitter
3381864	NM_000297.4(PKD2):c.128del (p.Pro43fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3382039	NM_000297.4(PKD2):c.428del (p.Gly143fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3383242	NM_000297.4(PKD2):c.129_147del (p.Gly45fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3591330	NM_000297.4(PKD2):c.113_127delinsGCCT (p.Ala38fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3591333	NM_000297.4(PKD2):c.193dup (p.Arg65fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3591335	NM_000297.4(PKD2):c.242C>A (p.Ser81Ter)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
3591336	NM_000297.4(PKD2):c.252_253delinsAT (p.Gln85Ter)	LOC129992813	Pathogenic	criteria provided, single submitter
3591339	NM_000297.4(PKD2):c.339del (p.Met114fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3591343	NM_000297.4(PKD2):c.468_486dup (p.Pro163fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3591344	NM_000297.4(PKD2):c.498_511del (p.Ser166fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3591345	NM_000297.4(PKD2):c.503delinsGGG (p.Val168fs)	LOC129992813	Pathogenic	criteria provided, single submitter
3591350	NM_000297.4(PKD2):c.547C>T (p.Gln183Ter)	LOC129992813	Pathogenic	criteria provided, single submitter
3720581	NM_000297.4(PKD2):c.203del (p.Pro68fs)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
3728760	NM_000297.4(PKD2):c.73_124dup (p.Ala42fs)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
373955	NM_000297.4(PKD2):c.357_364delinsTAGGACG (p.Pro120fs)	LOC129992813	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PKD2	Definitive	Autosomal dominant	autosomal dominant polycystic kidney disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PKD2	Orphanet:730	Autosomal dominant polycystic kidney disease
FAM13A	Orphanet:2032	Idiopathic pulmonary fibrosis
PKD1	Orphanet:730	Autosomal dominant polycystic kidney disease
PKD1	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
PRKD1	Orphanet:276145	Malignant epithelial tumor of salivary glands
PRKD1	Orphanet:708019	Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome
RAD51D	Orphanet:1331	Familial prostate cancer
RAD51D	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PKD2	HGNC:9009	ENSG00000118762	Q13563	Polycystin-2	gencc,clinvar
FAM13A	HGNC:19367	ENSG00000138640	O94988	Protein FAM13A	clinvar
MIR6511B1	HGNC:50228	ENSG00000284008		microRNA 6511b-1	clinvar
PKD1	HGNC:9008	ENSG00000008710	P98161	Polycystin-1	clinvar
PRKD1	HGNC:9407	ENSG00000184304	Q15139	Serine/threonine-protein kinase D1	clinvar
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PKD2	Polycystin-2	Forms a nonselective cation channel.
PKD1	Polycystin-1	Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B.
PRKD1	Serine/threonine-protein kinase D1	Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and tr…
RAD51D	DNA repair protein RAD51 homolog 4	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	4.9×	0.297
Kinase	1	4.6×	0.297
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PKD2	Other/Unknown	no		EF_hand_dom, PKD_2, EF-hand-dom_pair
FAM13A	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, FAM13
MIR6511B1	Other/Unknown	no
PKD1	Antibody/Immunoglobulin	yes		GPS, LRRNT, PC1
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE
RAD51D	Other/Unknown	no		AAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
oocyte	2
blood vessel layer	1
saphenous vein	1
jejunal mucosa	1
secondary oocyte	1
Ammon’s horn	1
sural nerve	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
seminal vesicle	1
thoracic aorta	1
ventricular zone	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PKD2	288	ubiquitous	marker	blood vessel layer, calcaneal tendon, saphenous vein
FAM13A	293	ubiquitous	marker	secondary oocyte, oocyte, jejunal mucosa
MIR6511B1	46		yes	sural nerve, calcaneal tendon, Ammon’s horn
PKD1	290		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta
RAD51D	187	ubiquitous	yes	sperm, male germ cell, oocyte

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAD51D	3,089
PRKD1	2,131
PKD2	1,644
PKD1	1,370
FAM13A	830
MIR6511B1	0

Intra-cohort edges

A	B	Sources
PKD1	PKD2	biogrid_interaction, intact, string_interaction
PKD1	PRKD1	string_interaction
PKD2	PRKD1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PKD2	Q13563	31
RAD51D	O75771	17
PKD1	P98161	13

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRKD1	Q15139	68.99
FAM13A	O94988	61.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 6 evidence-associated genes (5 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
VxPx cargo-targeting to cilium	2	207.6×	6e-04	PKD2, PKD1
Impaired BRCA2 binding to PALB2	1	91.4×	0.031	RAD51D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	84.6×	0.031	RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	84.6×	0.031	RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	84.6×	0.031	RAD51D
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	78.8×	0.031	RAD51D
Homologous DNA Pairing and Strand Exchange	1	76.1×	0.031	RAD51D
Resolution of D-loop Structures through Holliday Junction Intermediates	1	60.1×	0.031	RAD51D
Sphingolipid de novo biosynthesis	1	57.1×	0.031	PRKD1
Presynaptic phase of homologous DNA pairing and strand exchange	1	54.4×	0.031	RAD51D
HDR through Homologous Recombination (HRR)	1	38.1×	0.038	RAD51D
TP53 Regulates Transcription of DNA Repair Genes	1	36.2×	0.038	RAD51D
Sphingolipid metabolism	1	33.6×	0.038	PRKD1
RHOA GTPase cycle	1	14.9×	0.079	FAM13A
RAC1 GTPase cycle	1	12.2×	0.090	FAM13A
Metabolism of lipids	1	6.3×	0.158	PRKD1
Metabolism	1	2.3×	0.362	PRKD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mesonephric tubule development	2	3370.4×	1e-05	PKD2, PKD1
metanephric ascending thin limb development	2	1685.2×	3e-05	PKD2, PKD1
mesonephric duct development	2	1348.2×	3e-05	PKD2, PKD1
placenta blood vessel development	2	561.7×	2e-04	PKD2, PKD1
detection of mechanical stimulus	2	481.5×	2e-04	PKD2, PKD1
protein heterotetramerization	2	421.3×	2e-04	PKD2, PKD1
embryonic placenta development	2	306.4×	3e-04	PKD2, PKD1
regulation of cell cycle	3	44.7×	4e-04	PKD2, PKD1, RAD51D
neural tube development	2	210.7×	5e-04	PKD2, PKD1
spinal cord development	2	204.3×	5e-04	PKD2, PKD1
cell surface receptor signaling pathway via JAK-STAT	2	116.2×	0.001	PKD2, PKD1
metanephric cortex development	1	3370.4×	0.002	PKD2
metanephric cortical collecting duct development	1	3370.4×	0.002	PKD2
metanephric distal tubule development	1	3370.4×	0.002	PKD2
metanephric distal tubule morphogenesis	1	3370.4×	0.002	PKD1
liver development	2	88.7×	0.002	PKD2, PKD1
calcium ion transmembrane transport	2	84.3×	0.002	PKD2, PKD1
calcium ion transport	2	72.5×	0.002	PKD2, PKD1
regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril	1	1685.2×	0.004	PRKD1
renal artery morphogenesis	1	1685.2×	0.004	PKD2
nitrogen cycle metabolic process	1	1685.2×	0.004	PKD1
metanephric smooth muscle tissue development	1	1685.2×	0.004	PKD2
detection of nodal flow	1	1123.5×	0.005	PKD2
lymph vessel morphogenesis	1	1123.5×	0.005	PKD1
cellular response to hydrostatic pressure	1	1123.5×	0.005	PKD2
metanephric proximal tubule development	1	1123.5×	0.005	PKD1
calcium-independent cell-matrix adhesion	1	842.6×	0.005	PKD1
metanephric part of ureteric bud development	1	842.6×	0.005	PKD2
DNA strand invasion	1	842.6×	0.005	RAD51D
renal tubule morphogenesis	1	842.6×	0.005	PKD2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 3 of 6 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PRKD1	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKD1	26	4
PKD2	0	0
FAM13A	0	0
MIR6511B1	0	0
PKD1	0	0
RAD51D	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PRKD1	660	Binding:650, Functional:10
PKD1	27	Binding:27
PKD2	12	Binding:12

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKD1	2.7.11.13	protein kinase C

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PRKD1	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

26 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PKD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	PKD2, FAM13A, MIR6511B1, RAD51D

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1
PKD2	12	—
FAM13A	0	—
MIR6511B1	0	—
RAD51D	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.